Anti-acne composition containing a Poria cocos wolf extract

ABSTRACT

The invention concerns the use of an organic or hydro-organic extract of Poria cocos Wolf fungi for the preparation of a cosmetic and/or pharmaceutical composition, in particular a dermatological composition, for the treatment of acne and oily skin. 
     The preferred concentration of Poria cocos extract is in the range 0.001% to 5% by weight with respect to the total weight of the final composition. 
     Cosmetic or pharmaceutical compositions, in particular dermatological compositions, can be prepared for the effective treatment of acne and oily skin.

The present invention essentially concerns the use of a Poria cocos Wolffungus extract for the preparation of a cosmetic or pharmaceuticalcomposition, in particular a dermatological composition, for thetreatment of acne or oily skin, and a cosmetic treatment method.

The article in "Revue Bulletin de la Societe Chimique de France" (1980,No. 9-10, pp 473-477) describes the use of Poria cocos Wolf fungusextracts, more particularly triterpenes contained in these extracts,which have cytotoxic activity for the treatment of tumors.

Further, the database Excerpta Medica contains an English abstract ofthe Japanese review "Japan Journal of Pharmacology" (1992), volume 59(1), pp 89-96, which describes an antinephritic activity in a Poriacocos Wolf fungus extract.

Still further, published Japanese application number JP-A-1/038010 POLAdescribes a cosmetic composition for encouraging hair restoration andhair growth containing, among a number of active ingredients, an organicextract, in particular an alcoholic extract, of Poria cocos Wolf fungi.

Within the context of the present invention, we have unexpectedlydiscovered that organic or hydro-organic extracts of Poria cocos Wolffungi exhibit a novel anti-ache activity and an oily skin controllingactivity.

The aim of the present invention is thus to solve the novel technicalproblem with a solution which provides novel cosmetic or pharmaceuticalformulations, in particular dermatological compositions, with ananti-acne and/or oily skin control activity in a simple, reproducible,inexpensive manner which can be used on an industrial scale andcosmetically and/or pharmaceutically.

The present invention satisfactorily solves this novel technical problemfor the first time.

In a first aspect, therefore, the present invention concerns the use ofan organic or hydro-organic extract of Poria cocos Wolf fungi for themanufacture of a cosmetic and/or pharmaceutical composition, inparticular a dermatological composition, for the treatment of acne andoily skin.

Within the context of the invention, the expression "hydro-organicextract" means an extract obtained from a mixture of water and anorganic solvent which is miscible with water. In particular, within thecontext of the present invention, a hydro-alcoholic mixture ispreferably used, such as a hydro-ethanolic or a hydro-methanolicmixture, again preferably containing at least 50% by weight of alcoholwith respect to the total weight of the hydro-alcoholic mixture.

In a particular embodiment, an alcoholic extract is used, in particularan entirely ethanolic extract, or a hydro-alcoholic extract such as ahydro-ethanolic or hydro-methanolic extract of Poria cocos Wolf.

In another particular embodiment, the concentration of Poria cocosextract is in the range 0.001% to 5% by weight with respect to the totalweight of the final composition.

In yet another particular embodiment, the extract is at least partiallyincorporated into hydrated lamellar lipid phases or into liposomes.

In a still further particular embodiment, the Poria cocos extract iscombined with at least one other active ingredient, preferably selectedfrom the group consisting of a seboregulatory substance, an antisepticsubstance, an anticomedo substance and an anti-inflammatory substance.

In still another particular embodiment, the seboregulatory substance isan extract of licorice, glycyrrhiza glabra.

In a further particular embodiment, the antiseptic substance is ananti-corynebacterium substance such as hexamidine diisethionate, whichis commercially available, an isodon japonicus extract, which iscommercially available, clindamycin, or erythromycin.

In still another particular embodiment, the anticomedo substance isselected from the group consisting of acid vitamin A, vitamin A and itsderivatives such as the acetate, palmirate, propionate and azelaic acid.

In still another particular embodiment, the anti-inflammatory substanceis selected from the group consisting of ammonium glycyrrhyzinate,glycyrrhetinic acid, a-bisabolol, tocopherol phosphate and a corticoid.

In a second aspect, the present invention also concerns a method for thecosmetic treatment of oily skin, characterized in that an effectivequantity of an organic or hydro-organic extract of Poria cocos Wolffungi is topically applied to the oily zones of the skin, the effectivequantity generally being in a cosmetically or dermatologicallyacceptable excipient.

In a particular implementation, a cosmetic composition containing 0.001%to 5% by weight of the Poria cocos Wolf extract is applied.

In a further particular implementation, a cosmetic compositioncontaining an alcoholic extract, in particular an entirely ethanolicextract, or a hydro-alcoholic extract such as a hydro-ethanolic or ahydro-methanolic extract of Poria cocos Wolf fungi is applied.

In a still further particular implementation, the Poria cocos Wolfextract is at least partially incorporated into hydrated lamellar phasesor into liposomes.

Other aims, characteristics and advantages of the invention will becomeclear from the following description made with reference to variousexamples and activity tests, given simply by way of illustration andwhich does not in any way limit the scope of the invention.

In one or other of the preceding aspects of the invention, the organicextraction solvent is preferably an alcoholic extract, in particularselected from the group consisting of methanol, ethanol, butyleneglycoland propyleneglycol. These solvents can advantageously be used alone orin a mixture. They may also be used mixed with water. Some extracts arecommercially available, in particular a butyleneglycol extract of Poriacocos Wolf sold by the Japanese company Maruzen under the trade nameHoelen BG.

It should also be noted that for any of the preceding aspects of theinvention, the extract can be conventionally formulated in cosmetic orpharmaceutical compositions, in particular dermatological compositions,for example in the form of a gel, cream, emulsion or milk, for thetreatment of oily skin or skin subject to acne, or for the treatment ofacne.

Unless otherwise indicated, the percentages are given by weight, inparticular in the examples and in the claims.

EXAMPLE 1 Manufacture of an Ethanolic Extract of Poria cocos Wolf Fungi

Commercially available Poria cocos Wolf fungus was ground to increaseits contact surface with the solvent. This base material was extractedat 40° C. with ethanol using a base material/solvent proportion of 20g/l to 100 g/l. The extract was concentrated under vacuum.

This extract was termed extract I₁ of the invention.

EXAMPLE 2 Establishing the Inhibiting Activity of a Poria cocos WolfExtract on 5a-reductase Enzyme, an Enzyme Involved in Acne and Oily Skin

This test was based on the method of inhibiting 5a-reductase enzyme,which transforms testosterone to dihydrotestosterone, described in thereview J. I. D., (1987), 89, pp 87-92.

The skilled person is well aware that the formation ofdihydrotestosterone from testosterone, in particular under the action of5a-reductase enzyme, is involved in acne and oily skin and thatinhibition of this enzyme can effectively combat acne and oily skin.Thus establishing, for any active ingredient, a significant inhibitionof 5a-reductase enzyme activity is an appropriate test for determiningan anti-acne and oily skin control activity. Further, this test isrecognized by the skilled person as being reliable in in vitro testscarried out using the method described in the literature cited above.

In accordance with the literature, the test used an inoculum of normalhuman prepuce fibroblasts.

This fibroblast inoculum was cultured in a E 199 C medium (Techgen,France) to which 1% of foetal calf serum was added, in a proportion of10000 fibroblast cells per microplate hole. 0.1 μCi of testosteronelabelled with tritium was also added to each of these holes, to identifythe metabolites formed in contact with the fibroblasts by measuringtheir radioactivity.

Some holes acted as references and only received 1 ml of a 0.1% DMSOsolution, with no active ingredient. The other holes received the activeingredient to be tested, in this case an ethanolic extract of Poriacocos Wolf obtained as described in Example 1, in 1 ml of a 0.1% DMSO(dimethylsulfoxide) solution.

In each case, either for the reference or the active ingredient to betested, the contact time with the culture was 24 hours.

After 24 hours, the supernatant liquid was recovered, and the steroidswere extracted with 1 ml of an ethyl acetate-cyclohexane (1/1 by volume)extraction solvent. The extracted steroids were deposited on acommercial thin layer chromatography plate (Kieselgel 60F 254 DC Alufrom Merck®. The eluting system for the plate was a chloroform-methanolmixture, 98/2 volume/volume.

A scanner from Berthold, France, adapted to receive thin layerchromatography plates, was used to measure the radioactivity of thespots corresponding to testosterone and dihydrotestosterone.

The results are summarised in Table I.

                  TABLE I                                                         ______________________________________                                                                Dihydro-  Activity A                                  Product     Testosterone                                                                              testosterone                                                                            (%)                                         ______________________________________                                        Reference   47 ± 3%  28 ± 1%                                                                              0                                           (0.1% DMSO)                                                                   Product I.sub.1 of                                                                        61 ± 4%  20 ± 1%                                                                              29%                                         the invention                                                                 from Example 1                                                                (50 μg/l)                                                                  ______________________________________                                    

Activity A was determined using the following formula: ##EQU1## where:Tr represents the percentage of testosterone measured after 24 hours ofculture of the sample treated with the product from Example 1 (ethanolicextract of Poria cocos Wolf in accordance with the invention, in 0.1%

DMSO);

Te is the percentage of testosterone measured in the reference samplewhich received only 0.1% DMSO, also after 24 hours of culture.

It is clear from Table I that the alcoholic Poria cocos Wolf fungusextract had a significant activity for inhibiting 5a-reductase enzyme,correspondingly inhibiting the transformation of testosterone todihydrotestosterone and thus rendering this extract of particularly usefor the treatment of ache and oily skin.

EXAMPLE 3 Establishing the Seboregulatory Activity of Compositions ofthe Invention in Man

It is known that oily skin, even when not covered with ache, has a shinyand unsightly appearance due to the excessive production of sebum.

The present experiment in man aimed to show the activity of compositionsin accordance with the invention in regulating the secretion of sebum.

Three preparations, the compositions of which are shown in Table IIbelow, were tested.

Preparation B was a spray, preparation G was a cleansing gel andpreparation S was an oil control lotion.

                  TABLE II                                                        ______________________________________                                        Composition of tested preparations (percentages by weight)                                B(spray) G(gel)   S(lotion)                                       ______________________________________                                        Commercial butyleneglycol                                                                   0.3        0.06     3.6                                         Poria cocos Wolf extract                                                      (Hoelen BG)                                                                   Commercial isodon                                                                           0.15       0.03     1.8                                         Japonicus extract                                                             Hydro-ethanolic                                                                             0.05       0.01     0.6                                         Scutellaria baicalensis                                                       extract (Ichimaru Pharcos)                                                    Corn starch   0          0        8.0                                         Cosmetic excipient                                                                          qsp100.-   qsp100.- qsp100.                                     ______________________________________                                    

The experiment was carried out on 12 volunteers of average age 33 years,who had oily skin which was not subject to ache.

1. Evaluation of oil control effect

Before the experiment began, no cosmetics were used for a period ofthree days.

The oil control effect of regulating lotion S was evaluated afterapplication to half the face of a standard quantity, using a syringe.

Seborrhea and brightness of the skin were measured using a sebumeter anda chromameter respectively.

a-Sebumetry

A SM 810 Pc sebumeter from Courage and Khazaka was used.

The quantities of lipids at the cutaneous surface of the forehead weremeasured by sebumetry. The current level and the rate of sebaceousexcretion 30 minutes after degreasing were expressed as lipid indices.

The current level was measured before applications and every 2 hoursover a period of 8 hours to observe the kinetics.

The comparative results, expressed in lipid indices, are shown in TableIII

                  TABLE III                                                       ______________________________________                                        Kinetic study of seborrhea after treatment                                                  untreated  treated                                                            side       side                                                 ______________________________________                                        Time zero (application)                                                                       6.83 ± 3.71                                                                             7.50 ± 3.86                                   2 h after application                                                                         117.70 ± 46.13                                                                          88.67 ± 34.21                                 4 h after application                                                                         165.40 ± 39.33                                                                          147.83 ± 42.01                                6 h after application                                                                         203.90 ± 22.88                                                                          176.63 ± 26.63                                8 h after application                                                                         213.67 ± 30.00                                                                          181.70 ± 35.21                                ______________________________________                                    

The difference between the lipid indices obtained with the untreatedreference zone and the treated zone was significant at 2 hours, and wasmaintained at 4 hours, 6 hours and 8 hours.

It is clear from Table III that the application of regulating lotion Sin accordance with the invention significantly reduces the skinre-oiling after cleansing. The maximum current level was reached in 6hours.

b-Chromametry

The skin brightness of a treated cheek and an untreated cheek wasmeasured at the level of the corner of the nose by chromametry using aMinolta CR 200 Chromameter before application and then every 2 hoursover 8 hours.

The comparative skin brightness results are shown in Table IV.

                  TABLE IV                                                        ______________________________________                                        Skin brightness after treatment                                                              untreated treated                                                             side      side                                                 ______________________________________                                        Time zero (application)                                                                        62.41 ± 2.19                                                                           62.60 ± 1.88                                  2 h after application                                                                          62.31 ± 1.93                                                                           62.16 ± 2.22                                  4 h after application                                                                          62.28 ± 1.71                                                                           61.79 ± 1.59                                  6 h after application                                                                          62.09 ± 1.73                                                                           61.41 ± 1.60                                  8 h after application                                                                          62.25 ± 1.82                                                                           61.73 ± 2.10                                  ______________________________________                                    

The brightness parameter L on the treated side showed a reduction whichwas constant for the first 6 hours.

These developments are all statistically significant with respect to thecorresponding value at the moment of application of the preparation ofthe invention (time zero).

In conclusion, these tests have clearly demonstrated that thepreparation of the invention had an immediate effect, from its firstapplication, reducing the excessive flow of sebum and attenuating thebrightness of the skin, compared with the untreated skin zones.

2. Improvement in skin condition

The three preparations B, G and S were applied twice a day to theforehead. Cleansing was carried out with gel G followed by spraying withspray B then application of lotion S. The treatment was continued for 30days.

The improvement in the skin condition of 12 volunteers, all with oilyskin which was not subject to acne, was evaluated before, during and atthe end of a treatment period of 30 days.

A first improvement evaluation was made after 15 days of treatment, anda second after 30 days.

The intensity of seborrhea was divided into four levels:

level zero: practically no seborrhea

level 1 : low intensity seborrhea

level 2 : medium intensity seborrhea

level 3 : high intensity seborrhea

Table V below summarises the observations made on the 12 subjects:

                  TABLE V                                                         ______________________________________                                        Distribution of treated subjects before, during and at                        the end of the treatment as a function of the intensity                       of seborrhea                                                                                  After 15 days                                                                            after 30 days                                      Before use      of use     of use                                             ______________________________________                                        Level 0                                                                              0            0          0                                              Level 1                                                                              0            4          9                                              Level 2                                                                              10           8          3                                              Level 3                                                                              2            0          0                                              ______________________________________                                    

We observed an overall displacement within the group from the highintensity classes to the low intensity classes: the disappearance after15 days of subjects at level 3, a gradual reduction during the test ofthe numbers in level 2 and increase in level 1, which was in themajority at the end of the test.

A more precise analysis of the individual results from case to case,considering also intra-level developments, indicated the following:

after 15 days of treatment:

stationary state: 2 cases

reduction by one level: 5 cases

slight reduction (intra-level): 5 cases

after 30 days of treatment:

stationary state: 1 case

reduction by one level: 8 cases

slight reduction (intra-level): 3 cases

These clinical results, based on determining the current level ofintensity of sebum (before degreasing for measuring the rate) stronglyfavor the treatment: at the end of the test, 8 subjects out of 12 had anotably reduced level of seborrhea. The improvement was less substantialwith 3 subjects, and only one case appeared not to have been affected bythe treatment.

Thus the preparations of the invention are highly effective in man fortreating oily skin by regulating the production and flow of sebum. Theiruse thus contributes to improving the condition of the skin. The skinbecomes healthier and has a more pleasing appearance.

Examples will be given below of cosmetic or pharmaceutical compositions,in particular dermatological compositions, using a Poria cocos Wolfextract in accordance with the present invention.

EXAMPLE 4 Cosmetic Composition in the Form of a Treatment Gel

This cosmetic composition contained the following ingredients, byweight:

    ______________________________________                                        commercial butyleneglycol Poria                                                                       0.5     g                                             cocos Wolf extract from Hoelen BG                                             isodon extract (antiseptic)                                                                           0.5     g                                             ammonium glycyrrhizinate as an                                                                        0.3     g                                             anti-inflammatory substance                                                   Cremophor RH 40.sup.R   1       g                                             Carbopol 940.sup.R      1       g                                             fragranced aqueous excipient containing                                                               qsp 100 g                                             preservative                                                                  ______________________________________                                    

The extracts were added with the Cremophor RH 40® to the water to form50% of the composition, which was added to a gel of 2% Carbopolcontaining fragrances and preservatives, to form the final compositionwith the above formula.

The gel was applied twice a day to blackheads on skin with a tendency tosuffer from acne until the skin condition became good, namely afterabout three weeks.

EXAMPLE 5 Cosmetic Composition in the Form of a Cleansing Lotion

This composition had the following ingredients:

    ______________________________________                                        ethanolic extract of Poria cocos as                                                                   0.1     g                                             in Example 1                                                                  hexamidine diisethionate                                                                              0.1     g                                             hyaluronic acid         0.1     g                                             (moisturising substance)                                                      glycerin                0.2     g                                             fragranced aqueous excipient                                                                          qsp 100 g                                             containing preservative                                                       ______________________________________                                    

The ingredients were mixed together to obtain a homogeneous lotion whichwas used for twice-daily cleansing of oily skin.

This lotion was applied in the evening to zones of oily skin, afterremoving any makeup, as a preventative treatment and/or to treat theskin.

EXAMPLE 6 Dermatological Anti-Acne Composition

This composition had the following ingredients:

    ______________________________________                                        retinoic acid            0.05    g                                            Poria cocos extract I.sub.1 from Example 1                                                             0.5     g                                            clindamycin phosphate    1       g                                            propyleneglycol          5       g                                            ethanol                  30      g                                            gelled excipient containing Carbopol 940 ™                                                          qsp 100 g                                            and preservative                                                              ______________________________________                                    

This composition was prepared by firstly dissolving the differentingredients in ethanol to which the gelled excipient was added. Thecomposition could be used to pat onto local acne lesions until thelesions disappeared.

We claim:
 1. A method for the cosmetic treatment of oily areas of theskin, comprising topically applying to the oily areas of the skin aneffective amount of an organic or hydro-organic extract of Poria cocosWolf fungi in a cosmetically or dermatologically acceptable excipient.2. A method according to claim 1, characterized in that a cosmeticcomposition containing 0.001% to 5% by weight of the Poria cocos Wolfextract is applied.
 3. A method according to claim 1, comprisingapplying a cosmetic composition containing an alcoholic extract, or ahydro-alcoholic extract of Poria cocos Wolf fungi.
 4. A method accordingto claim 1, characterized in that the Poria cocos Wolf extract is atleast partially incorporated into hydrated lamellar phases or intoliposomes.
 5. A method according to claim 1, characterized in that thePoria cocos extract is combined with at least one other activeingredient, selected from the group consisting of a seboregulatorysubstance, an antiseptic substance, an anticomedo substance and ananti-inflammatory substance.
 6. A method according to claim 5, whereinthe seboregulatory substance is an extract of licorice.
 7. A methodaccording to claim 3, wherein the antiseptic substance is ananti-corynebacterium substance.
 8. A method according to claim 5,wherein the anticomedo substance is selected from the group consistingof acid vitamin A, vitamin A, vitamin A esters and azelaic acid.
 9. Amethod according to claim 5, characterized in that the anti-inflammatorysubstance is selected from the group consisting of ammoniumglycyrrhyzinate, glycyrrhetinic acid, a-bisabolol, tocopherol phosphateand a corticoid.
 10. A method for performing a skin treatment for acne,said method comprising:administering to an affected skin area aneffective amount for said treatment purpose of an organic orhydro-organic extract of Poria cocos wolf fungi.
 11. The method of claim10, wherein said Poria cocos Wolf extract is topically applied to saidskin area.
 12. The method of claim 10, wherein said Poria cocos wolfextract is applied to said affected skin area as a dermatologicalcomposition containing 0.001% to 5% by weight of the Poria cocos wolfextract in a dermatological acceptable excipient.
 13. The method ofclaim 10, wherein said Poria cocos Wolf extract is applied to saidaffected skin area as a dermatological composition containing analcoholic extract or a hydro-alcoholic extract of Poria cocos Wolf fungiin a dermatological acceptable excipient.
 14. The method of claim 13,wherein said alcoholic extract is an ethanolic extract and saidhydro-alcoholic extract is selected from the group consisting of ahydro-ethanolic extract and a hydro-methanolic extract.
 15. The methodof claim 10, wherein said Poria cocos Wolf extract is at least partiallyincorporated into hydrated lamellar phases or into liposomes.
 16. Themethod of claim 10, wherein said Poria cocos Wolf extract is combinedwith at least one active ingredient selected from the group consistingof a seboregulatory substance, an antiseptic substance, an anticomedosubstance and an anti-inflammatory substance.
 17. The method of claim16, wherein said seboregulatory substance is an extract of licorice. 18.The method of claim 16, wherein said antiseptic substance is ananti-corynebacterium substance.
 19. The method of claim 18, wherein saidanti-corynebacterium substance is selected from the group consisting ofhexamidine diisethionate, an isodon japonicus extract, clindamycin anderythromycin.
 20. The method of claim 16, wherein the anticomedosubstance is selected from the group consisting of acid vitamin A,vitamin A, vitamin A esters, and azelaic acid.
 21. The method of claim20, wherein said vitamin A esters are selected from the group consistingof vitamin A acetate, vitamin A palmitate and vitamin A propionate. 22.The method of claim 16, wherein said anti-inflammatory substance isselected from the group consisting of ammonium glycyrrhyzinate,glycyrrhetinic acid, a-bisabolol, tocopherol phosphate and a corticoid.23. The method of claim 3, wherein said alcoholic extract is an entirelyethanolic extract and said hydro-alcoholic extract is selected from thegroup consisting of a hydro-ethanolic extract and a hydro-methanolicextract.
 24. The method of claim 7, wherein said anti-corynebacteriumsubstance is selected from the group consisting of hexamidinediisethionate, an isodon japonicus extract, clindamycin anderythromycin.
 25. The method of claim 5, wherein said vitamin A estersare selected from the group consisting of vitamin A acetate, vitamin Apalmitate and vitamin A propionate.
 26. An anti-ache composition fortopical application to skin comprising an effective amount to treat acheof an organic or hydro-organic extract of Poria cocos Wolf fungi, saidPoria cocos Wolf extract being combined with at least one activeingredient selected from the group consisting of a seboregulatorysubstance, an antiseptic substance, an anticomedo substance and ananti-inflammatory substance; and a dermatologically topical acceptableexcipient.
 27. The anti-ache composition of claim 26, wherein saidseboregulatory substance is an extract of licorice.
 28. The anti-achecomposition of claim 26, wherein said antiseptic substance is ananti-corynebacterium substance.
 29. The anti-ache composition of claim28, wherein said anti-corynebacterium substance is selected from thegroup consisting of hexamidine diisethionate, an isodon japonicusextract, clindamycin and erythromycin.
 30. The anti-ache composition ofclaim 26, wherein the anticomedo substance is selected from the groupconsisting of acid vitamin A, vitamin A, vitamin A esters, and azelaicacid.
 31. The anti-ache composition of claim 30, wherein said vitamin Aesters are selected from the group consisting of vitamin A acetate,vitamin A palmirate and vitamin A propionate.
 32. The anti-achecomposition of claim 26, wherein said anti-inflammatory substance isselected from the group consisting of ammonium glycyrrhyzinate,glycyrrhetinic acid, a-bisabolol, tocopherol phosphate and a corticoid.33. The anti-acne composition of claim 26, wherein said amount of Poriacocos wolf extract in said composition is 0.001% to 5% by weightcomposition.
 34. The anti-ache composition of claim 26, wherein saidPoria cocos Wolf extract is an alcoholic extract or a hydro-alcoholicextract of Poria cocos Wolf fungi.
 35. The anti-ache composition ofclaim 26, wherein said alcoholic extract is an ethanotic extract andsaid hydro-alcoholic extract is selected from the group consisting of ahydro-ethanolic extract and a hydro-methanolic extract.
 36. Theanti-ache composition of claim 26, wherein said Poria cocos Wolf extractis at least partially incorporated into hydrated lamellar phases or intoliposomes.